J Cancer 2022; 13(5):1640-1651. doi:10.7150/jca.69210 This issue

Research Paper

Copy number amplification-activated long non-coding RNA LINC00662 epigenetically inhibits BIK by interacting with EZH2 to regulate tumorigenesis in non-small cell lung cancer

Chunluan Yuan1#, Yue Ding2#, Yan Zhuang3#, Chongguo Zhang4, Liang Han5✉, Wei Li6,7✉, Renhua Guo6✉, Erbao Zhang2,8✉

1. Department of Oncology, Lianyungang Clinical College of Nanjing Medical University, the First People's Hospital of Lianyungang, PR China
2. Department of Epidemiology, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing 211166, China
3. Department of Oncology, The Affiliated Cancer Hospital of Nanjing Medical University, Nanjing, Jiangsu, 210000, PR China
4. Department of Oncology, The second Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, 210000, PR China
5. Department of Oncology, Xuzhou Central Hospital, Xuzhou, Jiangsu, PR China
6. Department of Oncology, The first Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, 210000, PR China
7. Department of Oncology, Sir Run Run Hospital, Nanjing Medical University, Nanjing, Jiangsu, 210000, PR China
8. Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Nanjing 211166, China
#Chunluan Yuan, Yue Ding and Yan Zhuang contributed equally to this work and should be regarded as joint first authors.

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Citation:
Yuan C, Ding Y, Zhuang Y, Zhang C, Han L, Li W, Guo R, Zhang E. Copy number amplification-activated long non-coding RNA LINC00662 epigenetically inhibits BIK by interacting with EZH2 to regulate tumorigenesis in non-small cell lung cancer. J Cancer 2022; 13(5):1640-1651. doi:10.7150/jca.69210. Available from https://www.jcancer.org/v13p1640.htm

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Abstract

Graphic abstract

Recently, studies have shown that lncRNAs play important roles in regulation of cancer cells proliferation, apoptosis and metastasis. Here, through systematic bioinformatics analysis and screening, we identified a long noncoding RNA LINC00662 with high copy number amplification in NSCLC. High expression of LINC00662 predicted a poorer survival. The exact sequence full-length of LINC00662 was determined by rapid amplification of cDNA ends (RACE). We also found that LINC00662 could regulate lung cancer cell proliferation both in vitro and in vivo. Mechanically, we obtained global expression profile that respond to LINC00662 knockdown through RNA-Seq analysis. And we found that LINC00662 could bind to EZH2 and recruit EZH2 to the promoter regions of BIK, regulating the level of H3K27me3 in the BIK promoter, thus epigenetically repressing BIK expression. Our results shown that lncRNA LINC00662, driven by copy number amplification, promotes tumorigenesis by EZH2/BIK cell axis, indicating that it was a potential molecular target of NSCLC.

Keywords: Gene amplification, LINC00662, tumorigenesis, NSCLC